Necroptosis activation is associated with greater methylene blue-photodynamic therapy-induced cytotoxicity in human pancreatic ductal adenocarcinoma cells.
Daria R Q de AlmeidaAncély F Dos SantosRosangela A M WailemannLetícia F TerraVinícius M GomesGabriel S AriniEster R M BertoldiEduardo M ReisMaurício S BaptistaLeticia LabriolaPublished in: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (2022)
Pancreatic ductal adenocarcinomas (PDAC) are the fourth leading cause of death due to neoplasms. In view of the urgent need of effective treatments for PDAC, photodynamic therapy (PDT) appears as a promising alternative. However, its efficacy against PDAC and the mechanisms involved in cell death induction remain unclear. In this study, we set out to evaluate PDT's cytotoxicity using methylene blue (MB) as a photosensitizer (PS) (MB-PDT) and to evaluate the contribution of necroptosis in its effect in human PDAC cells. Our results demonstrated that MB-PDT induced significant death of different human PDAC models presenting two different susceptibility profiles. This effect was independent of MB uptake or its subcellular localization. We found that the ability of triggering necroptosis was determinant to increase the treatment efficiency. Analysis of single cell RNA-seq data from normal and neoplastic human pancreatic tissues showed that specific necroptosis proteins RIPK1, RIPK3 and MLKL presented significant higher expression levels in cells displaying a transformed phenotype providing further support to the use of approaches that activate necroptosis, like MB-PDT, as useful adjunct to surgery of PDAC to tackle the problem of microscopic residual disease as well as to minimize the chance of local and metastatic recurrence.
Keyphrases
- photodynamic therapy
- endothelial cells
- rna seq
- single cell
- induced apoptosis
- cell cycle arrest
- fluorescence imaging
- cell death
- high glucose
- pluripotent stem cells
- minimally invasive
- poor prognosis
- oxidative stress
- endoplasmic reticulum stress
- high throughput
- coronary artery disease
- case report
- drug induced
- acute coronary syndrome
- electronic health record
- signaling pathway
- smoking cessation
- percutaneous coronary intervention
- pi k akt
- replacement therapy